Research
Though RVCL is a rare genetic disorder, we strive to promote education, identification, and research generation.
We are determined to find a cure…
for Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL) and maintain long-term ongoing research grants with the University of Pennsylvania, The university of Michigan and Washington University. The space between scientific potential and human application can broadly be categorized as “academic research.” Without this important bridge, new advancements would cease to exist, hope would wane, and RVCL would continue unchecked. Fortunately, scientific progress exists, and we are excited to be a part of such a revolution. Favor fortunes the brave, and we love to support researchers who have innovative ideas and projects that may one day clinically benefit RVCL patients.
Currently, we are supporting several active research projects which have the potential for great knowledge to be gained and clinical advancements achieved.
Institutional Partners
Institutional Partner: UPenn
The RVCL Research Center at Penn is directed by Dr. Jonathan Miner, a rheumatologist with an extensive publication record in studies of rare rheumatic diseases. Dr. Miner currently directs a research laboratory that is supported by the National Institutes of Health and by the Clayco Foundation. Dr. Miner initiated a clinical trial of Crizanlizumab for RVCL, which is currently being conducted at Penn and WashU. Additionally, Dr. Miner leads a multidisciplinary team that cares for RVCL patients from around the world. The Miner laboratory collaborates with investigators from around the world to develop personalized medicines for RVCL.
Institutional Partner: WashU
RVCL was discovered at WashU in the late 1980s, and the disease-causing mutation was reported in 2007 by the laboratory of Dr. John Atkinson. Until recently, RVCL was referred to by other names including CRV, HERNS, and CHARIOT. WashU stroke neurologist Dr. Andria Ford currently cares for RVCL patients from around the United States and directs clinical research efforts at WashU. Dr. Ford also collaborates with physicians in multiple other subspecialties in the care of RVCL patients. In the laboratory, WashU researcher Dennis Hourcade collaborates with Dr. Miner at Penn in an NIH-funded study of the TREX1 gene.
Active Research Awards
Research Award: Washington University in St. Louis
Dr. Rajendra Apte M.D, Ph.D
Determining the extent to which retinal changes can be used as an RVCL diagnostic biomarker, and explore how new therapies may benefit overall eye health in RVCL patients.
It has been well established that RVCL patients suffer from retinal lesions and associated problems, though the extent and measurability of these retinal changes are still not fully understood. If further studied, it is possible that a more conclusive ‘retinal signature’ could be discovered that may help diagnose future RVCL patients in a quicker, more beneficial manner. In addition to diagnosability, better detailed understanding of RVCL associated eye problems may help guide treatment options and responses.
Research Award: The University of Edinburgh
Dr. David Hunt M.D, Ph.D
Developing a better model which mimics physiological human RVCL so that future therapeutic studies can be expedited.
In a sense, RVCL is a disease largely due to collapse of the microvascular system all over the body, which then causes a variety of observed symptoms. However, an RVCL model which mimics this collapse does not adequately exist, making it difficult to truly measure disease progression traits and how various treatments may benefit this underlying issue.The development of this ‘microfluidic, vascular’ RVCL model system would provide a significant tool for future study and help progress the best treatment options to the clinic for subsequent human study.
Research Award: The Institut Curie
Dr. Nicolas Manel Ph.D
Determining if RVCL is caused or exacerbated by unique DNA damage
It is a mutation in the TREX1 code and the accidental “free floating” nature of the TREX1 protein that leads to RVCL, versus the membrane-tethered Trex-1 protein in healthy individuals. To date, it is still not known why this free nature of Trex-1 causes such problems, such as vascular collapse and RVCL-associated demise. A portion of the Trex-1 protein is a DNase, a section capable of degrading DNA. In the RVCL condition, it is possible that it is this dysregulated DNAse that is inappropriately degrading important signals and causing or exacerbating the condition. The research here will investigate this possibility, which would represent an important finding as it would help to point future studies towards this functional area for therapeutic intervention.
Research Award: Washington University in St. Louis
Dr. Chao Zhou Ph.D
Developing a quicker RVCL drug-screening platform
As of today, there exist a nearly incalculable number of drugs with more constantly being created. It is possible that one of these existing drugs or a soon-to-exist drug will be beneficial in treating RVCL, however the ability to test such drugs is drastically limited by number of patients, insufficient models, and lack of time. By using the popular genetic screening system of the fruit fly, a system that can allow for genetic condition and drug testing at rapid pace, these efforts can be greatly expanded. The research here will begin with creation of the genetic system, and then subsequent vast analysis of potential therapeutic targets.
Publications
The discovery of RVCL (also known by other names including RVCL-S, CRV, and HERNS):
Grand et al, published in Ophthalmology in 1988:
https://pubmed.ncbi.nlm.nih.gov/3174024/
Another early description of RVCL (here called HERNS):
Jen et al, published in Neurology in 1997:
https://pubmed.ncbi.nlm.nih.gov/9371916/
Systematic clinical characterization of RVCL:
Stam et al., published in Brain 2016:
https://pubmed.ncbi.nlm.nih.gov/27604306/
TREX1 mutations cause RVCL:
Richards et al., published in Nature Genetics in 2007:
https://pubmed.ncbi.nlm.nih.gov/17660820/
Biomarkers of RVCL:
Pelzer et al, published in Stroke in 2017:
https://pubmed.ncbi.nlm.nih.gov/29114091/
Progressive worsening of neurological disease in patients RVCL:
Ford et al., published in Neurology in 2020:
https://pubmed.ncbi.nlm.nih.gov/32887784/
A model of RVCL:
Mulder et al., published in Stroke in 2020:
https://pubmed.ncbi.nlm.nih.gov/31805844/
